Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 4 Genetic pathways, genes, and gastrointestinal disorders[17-32]

Pathway	Key genes	Associated disorders	Mechanism/role	Ref.
Wnt/β-catenin	APC, CTNNB1, AXIN2	Colorectal cancer, hepatocellular carcinoma (HCC), familial adenomatous polyposis	Controls cell proliferation and differentiation; mutation leads to uncontrolled growth	Li et al[17]
NF-κB	NFKB1, TNFAIP3, IKK complex	IBD (Crohn’s, UC), gastric cancer, colorectal cancer	Regulates inflammation, cell survival, immunity; chronic activation promotes inflammation and tumorigenesis	Peng et al[18]
TGF-β/SMAD	TGFBR2, SMAD4	Juvenile polyposis, CRC, pancreatic cancer	Controls growth inhibition and apoptosis; mutations cause evasion of tumor suppression	Hata and Chen[19]
JAK/STAT	JAK2, STAT3, STAT1	IBD, colitis-associated cancer	Regulates immune cell signaling and cytokine responses	Hu et al[20]
MAPK/ERK	KRAS, BRAF, EGFR	CRC, pancreatic cancer, gastric cancer	Regulates cell proliferation and survival; mutations oncogenic signaling	Guo et al[21]
PI3K/AKT/mTOR	PIK3CA, PTEN, AKT1, MTOR	CRC, gastric cancer, IBD	Promotes cell growth, metabolism, and angiogenesis; dysregulation contributes to tumor growth and inflammation	Glaviano et al[22]
Mismatch repair	MLH1, MSH2, MSH6, PMS2	Lynch syndrome, CRC, gastric cancer	Repairs DNA replication errors; loss leads to microsatellite instability (MSI)	Li[23]
P53 pathway	TP53	CRC, esophageal, gastric, HCC	Controls cell cycle arrest, apoptosis, DNA repair; mutations common in late cancer stages	Harris and Levine[24]
Hedgehog signaling	PTCH1, GLI1	Gastric cancer, GI developmental disorders	Controls tissue patterning and stem cell maintenance	Briscoe and Thérond[25]
Notch signaling	NOTCH1, DLL1, HES1	Colitis, CRC, esophageal cancer	Regulates differentiation, especially goblet cells; dysregulation affects intestinal homeostasis	Kopan[26]
Autophagy pathway	ATG16 L1, IRGM	Crohn’s disease, IBD-associated cancer	Maintains intracellular bacterial clearance and mucosal homeostasis	Yu et al[27]
Immune checkpoint pathway	PD-L1, CTLA4	MSI-high CRC, gastric cancer, IBD	Immune evasion in cancer; dysregulated tolerance in autoimmune GI diseases	He and Xu[28]
ER stress/UPR	XBP1, IRE1, PERK	IBD, Paneth cell dysfunction, CRC	Regulates response to unfolded proteins; chronic ER stress leads to inflammation and epithelial damage	Chen et al[29]
IL-23/Th17 pathway	IL23R, STAT3, RORC	Crohn’s disease, UC, CRC	Inflammatory cytokine signaling driving chronic inflammation	Bunte and Beikler[30]
Apoptosis/FAS-FASL	FAS, BAX, CASP8	Colitis-associated cancer, gastric cancer	Regulates programmed cell death; evasion supports tumor survival	Waring and Müllbacher[31]
DNA repair pathways (base/nucleotide excision)	OGG1, XPA, POLB	CRC, gastric cancer	Repair oxidative and chemical DNA damage; defects genomic instability	Kumar et al[32]

NF-κB: Nuclear factor kappa-B; TGF-β: Transforming growth factor-beta; JAK: Janus tyrosine kinase; STAT: Signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; ERK: Extracellular regulated protein kinases; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; UPR: Unfolded protein response; ER: Endoplasmic reticulum; IL: Interleukin; Th: T helper; HCC: Hepatocellular carcinoma; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CRC: Colorectal cancer; GI: Gastrointestinal; MSI: Microsatellite instability.